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Reproductive state and choline intake influence enrichment of plasma lysophosphatidylcholine-DHA: a post hoc analysis of a controlled feeding trial.
Klatt, KC, McDougall, MQ, Malysheva, OV, Brenna, JT, Roberson, MS, Caudill, MA
The British journal of nutrition. 2019;(11):1221-1229
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Abstract
The major facilitator superfamily domain 2a protein was identified recently as a lysophosphatidylcholine (LPC) symporter with high affinity for LPC species enriched with DHA (LPC-DHA). To test the hypothesis that reproductive state and choline intake influence plasma LPC-DHA, we performed a post hoc analysis of samples available through 10 weeks of a previously conducted feeding study, which provided two doses of choline (480 and 930 mg/d) to non-pregnant (n 21), third-trimester pregnant (n 26), and lactating (n 24) women; all participants consumed 200 mg of supplemental DHA and 22 % of their daily choline intake as 2H-labelled choline. The effects of reproductive state and choline intake on total LPC-DHA (expressed as a percentage of LPC) and plasma enrichments of labelled LPC and LPC-DHA were assessed using mixed and generalised linear models. Reproductive state interacted with time (P = 0·001) to influence total LPC-DHA, which significantly increased by week 10 in non-pregnant women, but not in pregnant or lactating women. Contrary to total LPC-DHA, patterns of labelled LPC-DHA enrichments were discordant between pregnant and lactating women (P < 0·05), suggestive of unique, reproductive state-specific mechanisms that result in reduced production and/or enhanced clearance of LPC-DHA during pregnancy and lactation. Regardless of the reproductive state, women consuming 930 v. 480 mg choline per d exhibited no change in total LPC-DHA but higher d3-LPC-DHA (P = 0·02), indicating that higher choline intakes favour the production of LPC-DHA from the phosphatidylethanolamine N-methyltransferase pathway of phosphatidylcholine biosynthesis. Our results warrant further investigation into the effect of reproductive state and dietary choline on LPC-DHA dynamics and its contribution to DHA status.
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Regulation of the activins-follistatins-inhibins axis by energy status: Impact on reproductive function.
Perakakis, N, Upadhyay, J, Ghaly, W, Chen, J, Chrysafi, P, Anastasilakis, AD, Mantzoros, CS
Metabolism: clinical and experimental. 2018;:240-249
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Abstract
BACKGROUND We have previously demonstrated that the adipose tissue derived hormone leptin controls reproductive function by regulating the hypothalamic-pituitary-gonadal axis in response to energy deficiency. Here, we evaluate the activins-follistatins-inhibins (AFI) axis during acute (short-term fasting in healthy people) and chronic energy deficiency (women with hypothalamic amenorrhea due to strenuous exercise [HA]) and investigate their relation to leptin and reproductive function in healthy subjects and subjects with HA. METHODS The AFI axis was investigated in: a) A double-blinded study in healthy subjects having three randomly assigned admissions, each time for four days: in the isocaloric fed state, complete fasting with placebo treatment, complete fasting with leptin replacement, b) A case-control study comparing women with HA vs healthy controls, c) An open-label interventional study investigating leptin treatment in women with HA over a period of up to three months, d) A randomized interventional trial investigating leptin treatment vs placebo in women with HA for nine months. RESULTS The circulating levels of activin A, activin B, follistatin and follistatin-like 3 change robustly in response to acute and chronic energy deficiency. Leptin replacement in acute energy deprivation does not affect the levels of these hormones suggesting an independent regulation by these two hormonal pathways. In chronic energy deficiency, leptin replacement restores only activin B levels, which are in turn associated with an increase in the number of dominant follicles. CONCLUSIONS We demonstrate for the first time that the AFI axis is affected both by acute and chronic energy deficiency. Partial restoration of a component of the axis, i.e. activin B only, through leptin replacement is associated with improved reproductive function in women with HA.
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An association study of established breast cancer reproductive and lifestyle risk factors with tumour subtype defined by the prognostic 70-gene expression signature (MammaPrint®).
Makama, M, Drukker, CA, Rutgers, EJT, Slaets, L, Cardoso, F, Rookus, MA, Tryfonidis, K, Van't Veer, LJ, Schmidt, MK
European journal of cancer (Oxford, England : 1990). 2017;:5-13
Abstract
BACKGROUND Reproductive and lifestyle factors influence both breast cancer risk and prognosis; this might be through breast cancer subtype. Subtypes defined by immunohistochemical hormone receptor markers and gene expression signatures are used to predict prognosis of breast cancer patients based on their tumour biology. We investigated the association between established breast cancer risk factors and the 70-gene prognostication signature in breast cancer patients. PATIENTS AND METHODS Standardised questionnaires were used to obtain information on established risk factors of breast cancer from the Dutch patients of the MINDACT trial. Clinical-pathological and genomic information were obtained from the trial database. Logistic regression analyses were used to estimate the associations between lifestyle risk factors and tumour prognostic subtypes, measured by the 70-gene MammaPrint® signature (i.e. low-risk or high-risk tumours). RESULTS Of the 1555 breast cancer patients included, 910 had low-risk and 645 had high-risk tumours. Current body mass index (BMI), age at menarche, age at first birth, age at menopause, hormonal contraceptive use and hormone replacement therapy use were not associated with MammaPrint®. In parous women, higher parity was associated with a lower risk (OR: 0.75, [95% confidence interval {CI}: 0.59-0.95] P = 0.018) and longer breastfeeding duration with a higher risk (OR: 1.03, [95% CI: 1.01-1.05] P = 0.005) of developing high-risk tumours; risk estimates were similar within oestrogen receptor-positive disease. After stratifying by menopausal status, the associations remained present in post-menopausal women. CONCLUSION Using prognostic gene expression profiles, we have indications that specific reproductive factors may be associated with prognostic tumour subtypes beyond hormone receptor status.
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Selenium Supplementation and the Effects on Reproductive Outcomes, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome.
Razavi, M, Jamilian, M, Kashan, ZF, Heidar, Z, Mohseni, M, Ghandi, Y, Bagherian, T, Asemi, Z
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2016;(3):185-90
Abstract
Selenium supplementation could be effective on reproductive outcomes, biomarkers of inflammation, and oxidative stress among women with polycystic ovary syndrome (PCOS). The aim of the study was to determine the effects of selenium supplementation on reproductive outcomes, biomarkers of inflammation, and oxidative stress in PCOS patients. The present randomized double-blind, placebo-controlled trial was conducted on 64 women aged 18-40 years old with PCOS at the clinic affiliated to Ardabil University of Medical Sciences, Ardabil, Iran. The participants were randomly assigned to 2 groups receiving either 200 μg selenium daily (n=32) or placebo (n=32) for 8 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were measured and compared both before and after the treatment. After 8 weeks of intervention, pregnancy rate in the selenium group was higher than in the placebo group: 18.8 (6/32) vs. 3.1% (1/32), p=0.04. In addition, alopecia (40.6 vs. 9.4%, p=0.004) and acne (46.9 vs. 12.5 %, p=0.003) decreased following the consumption of selenium supplements compared with placebo. Additionally, patients who received selenium supplements had significantly decreased serum dehydroepiandrosterone (DHEA) levels (p=0.02), hirsutism (modified Ferriman-Gallwey scores) (p<0.001), serum high sensitivity C-reactive protein (hs-CRP) (p=0.02), and plasma malondialdehyde (MDA) levels (p=0.01) compared with placebo. We did not observe any significant effects of taking selenium supplements on other hormonal profiles, nitric oxide (NO), and other biomarkers of oxidative stress. Taken together, selenium supplementation for 8 weeks among PCOS women had beneficial effects on reproductive outcomes, DHEA, hs-CRP, and MDA levels. Supporting Information for this article is available online at http://www.thieme-connect.de/products.
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Vitamin D Metabolism Varies among Women in Different Reproductive States Consuming the Same Intakes of Vitamin D and Related Nutrients.
Park, H, Brannon, PM, West, AA, Yan, J, Jiang, X, Perry, CA, Malysheva, OV, Mehta, S, Caudill, MA
The Journal of nutrition. 2016;(8):1537-45
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Abstract
BACKGROUND The impact of the reproductive state on vitamin D metabolism and requirements is uncertain in part because of a lack of studies with controlled dietary intakes of vitamin D and related nutrients. OBJECTIVE We aimed to quantify the impact of the reproductive state on a panel of vitamin D biomarkers among women of childbearing age consuming equivalent amounts of vitamin D and related nutrients. METHODS Nested within a feeding study providing 2 doses of choline, healthy pregnant (26-29 wk gestation; n = 26), lactating (5 wk postpartum; n = 28), and control (nonpregnant/nonlactating; n = 21) women consumed a single amount of vitamin D (511 ± 48 IU/d: 311 ± 48 IU/d from diet and 200 IU/d as supplemental cholecalciferol) and related nutrients (1.6 ± 0.4 g Ca/d and 1.9 ± 0.3 g P/d) for 10 wk. Vitamin D biomarkers were measured in blood obtained at baseline and study end, and differences in biomarker response among the reproductive groups were assessed with linear mixed models adjusted for influential covariates (e.g., body mass index, season, race/ethnicity). RESULTS At study end, pregnant women had higher (P < 0.01) circulating concentrations of 25-hydroxyvitamin D [25(OH)D; 30%], 1,25-dihydroxyvitamin D [1,25(OH)2D; 80%], vitamin D binding protein (67%), and C3 epimer of 25(OH)D3 (100%) than control women. Pregnant women also had higher (P ≤ 0.04) ratios of 25(OH)D to 24,25-dihydroxyvitamin D [24,25(OH)2D; 40%] and 1,25(OH)2D to 25(OH)D (50%) than control women. In contrast, no differences (P ≥ 0.15) in vitamin D biomarkers were detected between the lactating and control groups. Notably, the study vitamin D dose of 511 IU/d achieved vitamin D adequacy in most participants (95%) regardless of their reproductive state. CONCLUSIONS The higher concentrations of vitamin D biomarkers among pregnant women than among control women suggest that metabolic adaptations, likely involving the placenta, transpire to enhance vitamin D supply during pregnancy. The study findings also support the adequacy of the current vitamin D RDA of 600 IU for achieving serum 25(OH)D concentrations ≥50 nmol/L among women differing in their reproductive state. This trial was registered at clinicaltrials.gov as NCT01127022.
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A randomised trial to evaluate the effects of low-dose aspirin in gestation and reproduction: design and baseline characteristics.
Schisterman, EF, Silver, RM, Perkins, NJ, Mumford, SL, Whitcomb, BW, Stanford, JB, Lesher, LL, Faraggi, D, Wactawski-Wende, J, Browne, RW, et al
Paediatric and perinatal epidemiology. 2013;(6):598-609
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Abstract
BACKGROUND Low-dose aspirin (LDA) has been proposed to improve pregnancy outcomes in couples experiencing recurrent pregnancy loss. However, results from studies of LDA on pregnancy outcomes have been inconsistent, perhaps because most studies evaluated LDA-initiated post-conception. The purpose of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was to determine whether preconception-initiated LDA improves livebirth rates in women with one to two prior losses. METHODS We performed a multicentre, block randomised, double-blind, placebo-controlled trial. Study participants were recruited using community-based advertisements and physician referral to four university medical centres in the US (2006-12). Eligible women were aged 18-40 years actively trying to conceive, with one to two prior losses. Participants were randomised to receive daily LDA (81 mg/day) or a matching placebo, and all were provided with daily 400-mcg folic acid. Follow-up continued for ≤6 menstrual cycles while attempting to conceive. For those who conceived, treatment was continued until 36 weeks gestation. The primary outcome was the cumulative livebirth rate over the trial period. RESULTS There were 1228 women randomised (615 LDA, 613 placebo). Participants had a mean age of 28.7, were mostly white (95%), well educated (86% more than high school education), and employed (75%) with a household income >$100 000 annually (40%). The characteristics of those in the treatment and placebo arms were well balanced. CONCLUSIONS We describe the study design, recruitment, data collection, and baseline characteristics of participants enrolled in EAGeR, which aimed to determine the effect of LDA on livebirth and other pregnancy outcomes in these women.
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Effect of testosterone supplementation with and without a dual 5α-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial.
Bhasin, S, Travison, TG, Storer, TW, Lakshman, K, Kaushik, M, Mazer, NA, Ngyuen, AH, Davda, MN, Jara, H, Aakil, A, et al
JAMA. 2012;(9):931-9
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CONTEXT Steroid 5α-reductase inhibitors are used to treat benign prostatic hyperplasia and androgenic alopecia, but the role of 5α-dihydrotestosterone (DHT) in mediating testosterone's effects on muscle, sexual function, erythropoiesis, and other androgen-dependent processes remains poorly understood. OBJECTIVE To determine whether testosterone's effects on muscle mass, strength, sexual function, hematocrit level, prostate volume, sebum production, and lipid levels are attenuated when its conversion to DHT is blocked by dutasteride (an inhibitor of 5α-reductase type 1 and 2). DESIGN, SETTING, AND PATIENTS The 5α-Reductase Trial was a randomized controlled trial of healthy men aged 18 to 50 years comparing placebo plus testosterone enthanate with dutasteride plus testosterone enanthate from May 2005 through June 2010. INTERVENTIONS Eight treatment groups received 50, 125, 300, or 600 mg/wk of testosterone enanthate for 20 weeks plus placebo (4 groups) or 2.5 mg/d of dutasteride (4 groups). MAIN OUTCOME MEASURES The primary outcome was change in fat-free mass; secondary outcomes: changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels. RESULTS A total of 139 men were randomized; 102 completed the 20-week intervention. Men assigned to dutasteride were similar at baseline to those assigned to placebo. The mean fat-free mass gained by the dutasteride groups was 0.6 kg (95% CI, -0.1 to 1.2 kg) when receiving 50 mg/wk of testosterone enanthate, 2.6 kg (95% CI, 0.9 to 4.3 kg) for 125 mg/wk, 5.8 kg (95% CI, 4.8 to 6.9 kg) for 300 mg/wk, and 7.1 kg (95% CI, 6.0 to 8.2 kg) for 600 mg/wk. The mean fat-free mass gained by the placebo groups was 0.8 kg (95% CI, -0.1 to 1.7 kg) when receiving 50 mg/wk of testosterone enanthate, 3.5 kg (95% CI, 2.1 to 4.8 kg) for 125 mg/wk, 5.7 kg (95% CI, 4.8 to 6.5 kg) for 300 mg/wk, and 8.1 kg (95% CI, 6.7 to 9.5 kg) for 600 mg/wk. The dose-adjusted differences between the dutasteride and placebo groups for fat-free mass were not significant (P = .18). Changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels did not differ between groups. CONCLUSION Changes in fat-free mass in response to graded testosterone doses did not differ in men in whom DHT was suppressed by dutasteride from those treated with placebo, indicating that conversion of testosterone to DHT is not essential for mediating its anabolic effects on muscle. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00493987.
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The effect of a hypocaloric diet with and without exercise training on body composition, cardiometabolic risk profile, and reproductive function in overweight and obese women with polycystic ovary syndrome.
Thomson, RL, Buckley, JD, Noakes, M, Clifton, PM, Norman, RJ, Brinkworth, GD
The Journal of clinical endocrinology and metabolism. 2008;(9):3373-80
Abstract
CONTEXT In overweight women with polycystic ovary syndrome (PCOS), the benefits of the addition of exercise to an energy-restricted diet in further improving cardiometabolic risk factors and reproductive function has not been extensively studied. OBJECTIVE The objective was to evaluate the effects of aerobic and aerobic-resistance exercise when combined with an energy-restricted high protein diet (5000-6000 kJ/d) on metabolic risk factors and reproductive function in women with PCOS. DESIGN AND SETTING A 20-wk outpatient, randomized, parallel study was conducted in a metropolitan research clinic. PATIENTS AND INTERVENTION Ninety-four overweight and obese women with PCOS (age 29.3 +/- 0.7 yr; body mass index 36.1 +/- 0.5 kg/m2) were randomized to diet only (DO; n = 30), diet and aerobic exercise (DA; n = 31), or diet and combined aerobic-resistance exercise (DC; n = 33). MAIN OUTCOME MEASURES Weight, body composition, cardiometabolic risk factors, hormonal status, menstrual cyclicity, and ovulatory function were assessed. RESULTS All interventions reduced weight (DO 8.9 +/- 1.6%, DA 10.6 +/- 1.7%, and DC 8.7 +/- 1.7%; P < 0.001) with no difference between treatments (P = 0.7, time x treatment). Fat mass decreased more (3 kg) and fat-free mass decreased less (2 kg) in DA and DC compared with DO (P < or = 0.03). Reductions in blood pressure (5.6/2.7 mm Hg), triglycerides (0.4 mmol/liter), total cholesterol (0.5 mmol/liter), low-density lipoprotein cholesterol (0.1 mmol/liter), glucose (0.2 mmol/liter), fasting insulin (4.3 mIU/liter), testosterone (0.4 nmol/liter), and free androgen index (2.8) (P < 0.001) and improvements in SHBG (7.0 nmol/liter) and reproductive function occurred in all groups, with no difference between treatments. CONCLUSION In overweight and obese women with PCOS, the addition of aerobic or combined aerobic-resistance exercise to an energy-restricted diet improved body composition but had no additional effect on improvements in cardiometabolic, hormonal, and reproductive outcomes relative to diet alone.
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Short-term meal replacements followed by dietary macronutrient restriction enhance weight loss in polycystic ovary syndrome.
Moran, LJ, Noakes, M, Clifton, PM, Wittert, GA, Williams, G, Norman, RJ
The American journal of clinical nutrition. 2006;(1):77-87
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BACKGROUND Polycystic ovary syndrome (PCOS), a common condition in women, improves with weight loss. Meal replacements in short-term weight loss and strategies for weight maintenance have not been investigated in PCOS. OBJECTIVE We compared in overweight women with PCOS the effects of meal replacements in short-term weight-loss and longer-term carbohydrate- or fat-restriction strategies on weight maintenance and improvements in reproductive and metabolic variables. DESIGN Overweight women with PCOS (n = 43; x +/- SD age: 32.1 +/- 5.2 y; weight: 96.1 +/- 18.4 kg) followed an 8-wk weight-loss regimen (2 meal replacements/d, 4904.4 +/- 127 kJ; phase 1) and then a 6-mo weight-maintenance carbohydrate- (<120 g/d) or fat- (<50 g/d) restriction regimen (phase 2). RESULTS Thirty-four women completed phase 1, and 23 women completed phase 2; the proportion of dropouts was similar in the 2 groups. During phase 1, significant (P < 0.05) reductions in weight (5.6 +/- 2.4 kg), waist circumference (6.1 +/- 2.5 cm), body fat (4.1 +/- 2.2 kg), insulin (2.8 +/- 1.1 mU/L), total testosterone (0.3 +/- 0.7 nmol/L), and free androgen index (3.1 +/- 4.6) occurred; these changes were sustained during phase 2. No significant differences between diet groups were seen for any variables. At 6 mo, both approaches resulted in a net weight loss of 4.7 +/- 4.6 kg. Improvements in menstrual cyclicity occurred for 16 (57.1%) of 28 subjects. CONCLUSIONS Meal replacements are an effective strategy for the short-term management of PCOS. Advice on moderate fat or carbohydrate restriction was equally effective in maintaining weight reduction and improving reproductive and metabolic variables.